Stability of peripheral blood immune markers in patients with asthma

Abstract

Background Asthma is a complex disease with variable course. Efforts to identify biomarkers to predict asthma severity, the course of disease and response to treatment have not been very successful so far. We have previous suggested that PAR-2 and CRTh2 expression on specific peripheral blood cell subtypes may be biomarkers of asthma severity. We reasoned that parameters that remain stable when asthma symptoms are controlled would be the most appropriate to evaluate for their utility to predict loss of asthma control and/or severity of the disease. Methods Nineteen stable asthmatics were recruited from the University of Alberta Asthma clinic and followed in clinic every 3 months for a total of 4 visits. Patients had spirometry and completed the ACQ questionnaire in every visit. Blood was drawn in every visit and analyzed for a number of immune parameters by flow cytometry. These parameters included PAR-2 and CRTh2 expression on monocyte subgroups and T lymphocytes respectively, as well as numbers of eosinophils, innate lymphoid type-2 cells (ILC2) and dendritic cells. Within person stability of immune and physiological parameters was calculated using the intraclass correlation (ICC) using R version 3.4.0. Results FEV 1 (% predicted), FEV 1 /FVC ratio, ACQ5 and ACQ7 did not differ significantly over the 4 visits, as would be expected for patients with stable asthma. Peripheral blood eosinophil numbers by Kimura stain and by flow cytometry showed ICC scores of 0.44 and 0.52 respectively, indicating moderate stability. The % of ILC2 cells in peripheral blood also showed moderate stability [ICC score of 0.45 (0.14–0.67)]. The stability for all other immune parameters was poor. Conclusion Among the peripheral blood immune parameters we studied, only numbers of eosinophils and ILC2 in peripheral blood were moderately stable over a year in stable asthmatics. Further studies are required to understand the reasons for the variability of the other cell types.

Th2 cell markers in peripheral blood increase during an acute asthma exacerbation

“…Our study shows that the number of Th2 cells (CD4 + CRTh2 + T cells) in peripheral blood during an asthma exacerbation correlates with asthma control and asthma quality of life measures, but not with pulmonary function parameters. This finding is in contrast to our previous report in a population of stable asthmatics that showed the number of Th2 cells in peripheral blood did not correlate with ACQ6 scores 20 . It is possible to speculate that the increased numbers of Th2 cells and possibly their activation status during an asthma exacerbation affect asthma control and subsequently quality of life in these subjects; especially if a previously reported 24 pathogenic phenotype of Th2 cells is overrepresented in patients during acute asthma exacerbations.…”

“…To study whether immune parameters during acute asthma exacerbations are different than during the stable phase of the disease, we compared data from the ED visits with those from a cohort of stable asthmatics we reported previously 20 ; all values used for comparison were taken from the fourth visit of the previous study.…”

The Biology of Prostaglandins and Their Role as a Target for Allergic Airway Disease Therapy

“…Moreover, mast cell-derived PGD 2 activated type-2 CD8 (+) T cells via the CRTH2 receptor, inducing migration and cytokine (IL-5 and IL-13) production in severe eosinophilic asthma [64]. Studies supporting these findings have shown that a larger population of CRTH2 (+) T cells was identified from the peripheral blood of patients with severe asthma, and allergen-specific Th2 cells could be identified by stable co-expression of CRTH2 [65][66][67]. PGE 2 has been proposed to induce Th2 responses by attenuating the production of IL-2 and IFN-γ by Th1 cells without enhancing the release of IL-4 by Th2 cells [26,68].…”

Scrophularia koraiensis Nakai Attenuates Allergic Airway Inflammation via Suppression of NF-κB and Enhancement of Nrf2/HO-1 Signaling

“…Elevated eosinophil numbers are considered major biomarkers of asthma [22]. Eosinophilia during asthma development is associated with pro-inflammatory cytokines such as IL-4, IL-5 and IL-13 [23,24].…”